Serum carboxypeptidaseA4 levels predict liver metastasis in colorectal carcinoma

// Lichao Sun 1 , Chunguang Guo 3 , Joseph Burnett 2 , Zhihua Yang 1 , Yuliang Ran 1 , Duxin Sun 2 1 State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, P.R. China 2 Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA 3 The Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences (CAMS), Beijing 100021, P.R. China Correspondence to: Lichao Sun, email: Prof_sunlichao@163.com Duxin Sun, email: duxins@umich.edu Keywords: CPA4, marker, liver metastasis, colorectal cancer, prognosis Received: August 16, 2016 Accepted: October 14, 2016 Published: October 21, 2016 ABSTRACT Hepatic metastasis is the most critical prognostic factor for colorectal cancer (CRC), and early detection of CRC liver metastasis can significantly improve cancer patient outcomes. In this study, we examined the levels of CPA4 in CRC samples, and assessed the potential of serum CPA4 as a biomarker for predicting CRC liver metastasis. CPA4 positivity was observed in 68.4% (130/190) colorectal cancer tissues, and significantly correlated with Depth of invasion, Lymph node metastasis, Distant metastasis and Stage. In addition, high CPA4 expression was associated with poor overall survival, and was an independent prognostic marker in patients with CRC. In CRC serum samples, serum CPA4 concentrations in CRC-M1(S) patients (3717.89 ± 375.98 pg/mL) were significantly increased as compared to in CRC-M1(H) patients (3692.12 ± 261.51 pg/mL), CRC patients without liver metastasis (2480.47 ± 507.90 pg/mL) or healthy controls (2183.7 ± 621.7 pg/mL) ( P < 0.05). Furthermore, high CPA4 concentration was significantly correlated with Distant metastasis, Lymph node involvement, Stage and poor overall survival of the patients with CRC. Logistic regression analysis revealed that serum CPA4 level and Lymph node metastasis were the significant parameters for predicting CRC liver metastasis. In leave-one-out-cross-validation, these two markers resulted in sensitivity (90.0%) and specificity (93.8%) for hepatic metastasis detection. Moreover, this combination could correctly classify 49 cases of the 50 CRC patients with heterochronous liver metastasis in an independent test set. Therefore, our results suggest that CPA4 is closely associated with CRC liver metastasis, and serum CPA4 concentration combined with lymph node involvement may be used as accurate predictors of liver metastasis in colorectal cancer.